3D Printed Silicon Nitride Porous PEEK Composite Spinal Cages for Anti-Infection

项目摘要-当颈部和背部疼痛变得难以治愈时，脊柱融合术是黄金标准 治疗。然而，高达12%的融合失败是由于感染，导致大量的个人和经济损失。 成本。在大多数情况下，这些感染与用于稳定融合的硬件有关。传统上讲 模压或机械加工的聚醚醚酮(PEEK)保持架由于PEEK的原因被广泛用于此目的 强度、与骨骼相当的弹性模数、生物兼容性和放射透明度。然而，传统的偷看 笼子和常见替代品容易发生脊椎感染。氮化硅(Si3N4)间隔物已用于 具有良好抗菌性能历史的其他脊柱应用(即，只有0.006的植入物具有 与感染相关)，与其他材料相比，它们提供了更好的骨整合。 不幸的是，Si3N4并不是稳定脊柱融合的理想材料，因为这种材料可能会受到 下沉和脆性断裂。在第一阶段，SINTX Technologies与德雷克塞尔大学合作 托马斯·杰斐逊大学将把Si3N4的抗菌和骨整合特性与 PEEK的强度和弹性，以开发新型3-D打印抗菌颈椎保持架。发展和 3DP Si3N4-PEEK颈椎融合器的商业化将解决临床上对 抗菌脊柱融合稳定器，促进骨整合，承受体内负荷，并促进 成像。目的1.设计一种满足ASTM静态载荷要求的3DP Si3N4-PEEK颈椎保持架 F2077。里程碑：展示3DP Si3N4-PEEK多孔材料的静态压缩、剪切和扭转强度 符合或超过ASTM F2077制定并基准的颈椎保持架指南的保持架 对于许多笼子制造商来说，在文献中。目的2.测定抗菌活性和成骨细胞 增殖/成熟作为Si3N4百分比的函数。里程碑：A&gt；1.5原木细菌减少 在保持成骨细胞增殖/成熟的同时进行定植。影响-该项目预计将 演示创建颈椎融合器的可行性，同时保留优越的放射学和 3DP-PEEK生物材料保持骨整合和抗菌性能的生物力学性能 Si3N4的性质。第二阶段的STTR或SBIR将把3DP Si3N4-PEEK颈椎融合器提升到支持IDE 研究，包括评估疲劳性，抗沉降性，和临床前的表现 全尺寸严格供能的活体模型。合理设计的抗菌脊椎保持架可靠地减少了 感染是至关重要的，特别是考虑到融合失败的个人和经济成本以及日益增长的 由于人口老龄化，美国脊柱融合手术的数量有所增加。进入第二阶段的里程碑- 交付3DP Si3N4-PEEK颈椎保持架，(1)满足ASTM F2077的静态载荷要求，(2) 满足骨整合的最低性能阈值，以及(3)满足最低性能阈值 具有抗菌活性。量化指标包括在该方法中。

PROJECT SUMMARY—When neck and back pain becomes intractable, spinal fusion is the gold-standard treatment. However, up to 12% of these fusions fail due to infection, resulting in substantial personal and financial costs. In most cases, these infections are associated with the hardware used to stabilize the fusion. Traditionally molded or machined polyether ether ketone (PEEK) cages are widely used for this purpose due to PEEK’s strength, elastic modulus comparable to bone, biocompatibility, and radiolucency. However, traditional PEEK cages and common alternatives are prone to spinal infection. Silicon nitride (Si3N4) spacers have been used in other spinal applications with an excellent antimicrobial performance history (i.e., only 0.006% of implants have been associated with infection), and they provide superior osseointegration compared to other materials. Unfortunately, Si3N4 is not ideal for stabilizing spinal fusions because the material may be susceptible to subsidence and brittle fracture. In this Phase I STTR, SINTX Technologies, in collaboration with Drexel University and Thomas Jefferson University, will combine the antimicrobial and osseointegrative properties of Si3N4 with the strength and elasticity of PEEK to develop novel 3-D-printed antimicrobial cervical cages. Development and commercialization of a 3DP Si3N4-PEEK cervical cage would address a critical unmet clinical need for an antimicrobial spinal fusion stabilizer that promotes osseointegration, withstands in vivo loading, and facilitates imaging. Aim 1. Design a 3DP Si3N4-PEEK cervical cage that meets the static loading requirements of ASTM F2077. Milestone: Demonstrate static compression, shear, and torsion strength of 3DP Si3N4-PEEK’s porous cages that meets or exceeds the guidelines for cervical cages established by ASTM F2077 and benchmarked for many cage manufacturers in the literature. Aim 2. Determine antibacterial activity and osteoblast proliferation/maturation as a function of Si3N4 percentage. Milestone: A >1.5 log reduction in bacterial colonization while retaining osteoblastic proliferation/maturation. Impact—This project is expected to demonstrate the feasibility of creating cervical cages that simultaneously retain the superior radiological and biomechanical qualities of 3DP PEEK biomaterials while preserving the osseointegrative and antimicrobial qualities of Si3N4. A Phase II STTR or SBIR would advance the 3DP Si3N4-PEEK cervical cage to IDE-enabling studies, including assessments of fatigue performance, subsidence resistance, and preclinical performance in a full-scale rigorously powered in vivo model. Rationally designed antibacterial spinal cages that reliably reduce infection are critical, especially given the personal and financial costs of failed fusions as well as the increasing numbers of spinal fusions in the US due to our aging population. Milestone for Progression to Phase II— Delivery of a 3DP Si3N4-PEEK cervical cage that (1) meets the static loading requirements of ASTM F2077, (2) meets minimum performance thresholds for osseointegration, and (3) meets minimum performance thresholds for antibacterial activity. Quantitative targets are included in the Approach.